Trachoma is the leading infectious cause of blindness, and, together with extraocular chlamydial infection, constitutes a major public health problem throughout the world. Our work so far has demonstrated the dichotomous role of the immune response in trachoma. On the one hand, there is evidence for protective immunity; while paradoxically, much of the disease process appears to be immunologically mediated. We have shown that the ocular disease is a delayed type hypersensitivity reaction to a chlamydia antigen released by viable chlamydia. Animals that have recovered from chlamydial infection have partial immunity to reinfection; tear IgA antibodies to chlamydial major outer membrane protein (MOMP, 39kD) appear to confer this protection. Preliminary purified MOMP vaccines which stimulate mucosal immunity are partially effective, but induce only a weak antibody response. The objective of this proposal will be to develop a safe and effective protective vaccine against chlamydial eye infection. Specifically, we will test synthetic and recombinant MOMP epitopes for efficacy in reducing clinical disease and follow the immunologic response during vaccination and after challenge to improve the efficacy of these candidate vaccines. We will conduct these studies in our monkey model of trachoma. At present, this is the only model that exists in which human chlamydial pathogens can be studies in an intact primate eye. We will follow the immune response to vaccination, and after infectious challenge by following the local and systemic, humoral, and cell-mediated responses. As part of this work, we will study the responsiveness of lymphocytes obtained from the conjunctiva and determine their subset and antigen specificity. Because of the similarities between ocular and extraocular chlamydial infection, advances in one area are likely to be highly relevant to the other.